We have clonally-developed several cell lines with three different growth characteristics, namely, slow growing, intermediate and fast growing, from the prostate epithelium of castrated rats. The present proposal is for further characterization and validation of these different cell lines. Two specific aims are proposed. Specific Aim 1 deals with the further characterization of the different cell lines: karyotyping, telomerase assay, ability to respond to growth-enhancing and growth-inhibitory factors, androgen responsiveness, and tumorigenicity. Specific Aim 2 will examine the role of integrins and extracellular matrix in the differentiation of epithelial cells from basal to luminal forms in the presence or absence of androgens. Although the molecular action of androgen in prostatic epithelial cells has been studied extensively, little is known on the role of integrins and extracellular matrix in differentiation of prostate epithelial cells. It is our hypothesis that androgen action (at least in differentiation) is mediated either directly or indirectly through the interaction of adhesion molecules of the epithelium and the extracellular matrices. The ultimate goal of this project is to develop prostatic epithelial cell lines of specific lineages that could be used as in vitro models for growth and differentiation of the prostate epithelium in both normal and abnormal states.